This project proposes to use the rat model to investigate the in utero effect of ultrasound exposure on various growth, developmental, and behavioral endpoints. The rat is chosen because of the large body of information available on the in utero effects of various toxic agents. Low birth weight and delays in weight gain (from day 1 to 28 post-parturition); behavioral effects (righting reflex, negative geotaxis, reflex suspension, continuous corridor exploration, and modified open field exploration); and morphometric findings (focusing on brain, thyroid, and pituitary, although other tissues and organs will be screened) will be correlated with numerous variables of in utero ultrasound exposure. The problem of collecting information on the bioeffects of ultrasound will be approached in the following stepwise fashion: 1) The effects of ultrasound at high exposure levels will be determined. This will be accomplished with non-clinical equipment designed to produce the highest intensity exposures possible (up to and including levels where thermal effects may become a factor). While these exposure levels will be unrealistic in terms of human exposure, they will serve to document whether in utero ultrasound can cause developmental problems; and will document the types of damage that one should look for at lower exposure levels. 2) The level of effects produced by exposure levels that might be achieved clinically will be determined. Assuming that these effects will be relatively minor and infrequent, it is essential that a) it is known what types of damage are expected, b) there is statistical analysis of the dose-related changes, and c) that the effects be matched against a positive control (e.g., low dose ionizing radiation). 3) The information gained above will allow the determination of thresholds for various effects, i.e., the level of exposure below which there is no evidence of damage. The kinetics of the dose-response function will also be described. 4) A comparison will be made of the risks (or lack of risk) from ultrasound exposure at reasonable clinical levels to the corresponding levels of risk from ionizing radiation. In this way, the question is addressed of whether in utero ultrasound exposure carries the potential for inducing long-lasting biological effects; and if so, exactly what that risk is.
| Norton, S; Kimler, B F; Mullenix, P J (1991) Progressive behavioral changes in rats after exposure to low levels of ionizing radiation in utero. Neurotoxicol Teratol 13:181-8 |
| Norton, S; Kimler, B F; Cytacki, E P et al. (1991) Prenatal and postnatal consequences in the brain and behavior of rats exposed to ultrasound in utero. J Ultrasound Med 10:69-75 |
| Norton, S; Kimler, B F (1990) Early effects of low doses of ionizing radiation on the fetal cerebral cortex in rats. Radiat Res 124:235-41 |
| Norton, S; Kimler, B F; Cytacki, E P et al. (1990) Acute response of fetal rat telencephalon to ultrasound exposure in utero. Exp Neurol 107:154-63 |
| Norton, S (1989) Correlation of cerebral cortical morphology with behavior. Toxicol Ind Health 5:247-55 |
| Norton, S; Kimler, B F (1988) Comparison of functional and morphological deficits in the rat after gestational exposure to ionizing radiation. Neurotoxicol Teratol 10:363-71 |
